ReferenceID 5658
Lycorine ameliorates bleomycin-induced pulmonary fibrosis via inhibiting NLRP3 inflammasome activation and pyroptosis
Pharmacol Res
Idiopathic pulmonary fibrosis (IPF) is a chronic and irreversible lung disease with limited therapeutic strategies. Lycorine (LYC), an alkaloid isolated from Amaryllidaceae family plants, exhibits effective anti-inflamma
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- Reference Id
- 5658
- Evidence Id
- 22248
- Core Evidence Id
- 22248
- Source Reference Id
- 4544
- Herb2 Reference Id
- HBREF005341
- Subject Paper Key
- HBIN034010_32428667
- Pubmed Id
- 32428667
- Doi
- 10.1016/j.phrs.2020.104884
- Paper Title
- Lycorine ameliorates bleomycin-induced pulmonary fibrosis via inhibiting NLRP3 inflammasome activation and pyroptosis
- Paper Abstract
- Idiopathic pulmonary fibrosis (IPF) is a chronic and irreversible lung disease with limited therapeutic strategies. Lycorine (LYC), an alkaloid isolated from Amaryllidaceae family plants, exhibits effective anti-inflammatory, antiviral, and anti-tumor activities. In this study, we attempted to determine the effect of LYC on bleomycin (BLM)-induced IPF and NLRP3 inflammasome activation. Our results demonstrated that the LYC treatment ameliorated BLM-induced pulmonary fibrosis and inflammation in mice. LYC inhibited active Caspase-1 expression and lactate dehydrogenase (LDH) release during BLM-induced acute lung injury (ALI) in mice. Furthermore, our in vitro assay showed that LYC inhibited LPS/Nigericin- or LPS/ATP-induced NACHT, LRP and PYD domains-containing protein 3 (NLRP3) inflammasome activation, and pyroptosis in bone marrow-derived macrophages (BMDMs). Mechanically, LYC could disturb the interaction of NLRP3 with apoptosis-associated speck-like protein containing a CARD (ASC) by targeting the pyrin domain (PYD) on Leu9, Leu50, and Thr53. Our findings indicate that LYC ameliorated BLM-induced pulmonary fibrosis by inhibiting NLRP3 inflammasome activation and pyroptosis through targeting the PYD domain of ASC. Thus, LYC might be a potential therapeutic agent for pulmonary inflammation and fibrosis.
- Journal
- Pharmacol Res
- Publish Year
- 2020
- Experiment Subject
- mouse
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Inflammation; Idiopathic Pulmonary Fibrosis; Pulmonary Inflammation; Chronic And Irreversible Lung Disease; Acute Lung Injury; Fibrosis; Pulmonary Fibrosis
- Paper Title Cn
- Paper Title En
- Lycorine ameliorates bleomycin-induced pulmonary fibrosis via inhibiting NLRP3 inflammasome activation and pyroptosis
- Bilingual Status
- semi_complete